The epidermis and the dermis, separated by the basal membrane, constitute the cutaneous covering on the hypoderm. The epidermis is the most superficial layer of the skin and provides its resistance and impermeability.
Although different types of cells coexist in the epidermis, keratinocytes make up the majority of this layer and play a role in the resistance provided by the mucocutaneous barrier. The core activity of these cells is the synthesis of keratins, which represent close to 90% of all the protein in the epidermis.
The dermis, the internal layer of the skin, is conjunctive tissue composed of cells (essentially fibroblasts) dispersed in a complex medium called the extracellular matrix (ECM). This matrix consists of collagen and elastin fibres, glycoproteins (fibronectin and laminin) and proteoglycans. The extracellular matrix serves as a structure for the cells, allowing tissues and organs to cohere in pluricellular organisms.
Interactions between the cells of the epidermis and the fibres of the dermis play a significant role in controlling cellular behaviour, such as in healing, for example, but also provide stability to the dermo-epidermal junction (DEJ), which anchors the epidermis to the dermis and forms a protective barrier. The DEJ acts at several levels. First, it serves as a mechanical support, using the collagen IV network to solidly anchor the epidermis to the dermis. It also plays a biological role by establishing direct relationships with the basal cells of the epidermis. It further serves as a significant reservoir for growth factors. Finally, it supports keratinocytes during the healing process.
The DEJ consists of two laminae: (A) The basal lamina, to which epidermal cells adhere. The basal lamina is itself composed of two layers: the lamina lucida and the lamina densa. This is where is found type IV collagen, proteoglycans and glycoproteins, components that are organized in the anchoring filaments that create the laminae. Laminins are glycoproteins that allow the keratinocytes to adhere to the basal lamina. Many laminins are present in the basal lamina, among which the most common are laminin-5, laminin-6 and laminin-7, and laminin-1. Laminin-5 (also known as laminin 332), a multi-purpose matrix protein, is the most commonly found laminin in the skin's basal membrane. It is the most common adherence protein for cells in the epidermis. Laminin-5 serves a double purpose: it can induce a strong and strategic cellular adherence or, on the contrary, it can produce a weak, temporary adherence for cellular migration. This property is well illustrated in the skin, since, although laminin-5 anchors the epidermis, it also plays a role in the migration of keratinocytes during the healing process. Studies of skin healing in vivo have shown greater expression of pre-laminin-5 in the ECM of keratinocytes located in the wound's colonization zone, indicating that the absence of proteolytic maturation fosters cellular migration. Laminin-5 further plays a key role in cellular restructuring and scar formation.
(B) The reticular lamina: Also known as the sub-lamina densa, it is connected to the dermis and consists of a dense matrix formed in part of collagen VII, III and I filaments and basic substances. Collagen VII, synthesized mainly by keratinocytes, is the major component of the sub-lamina densa and represents an essential anchoring fibre. Connected to the laminin-5 or collagen IV of the lamina densa, the anchoring fibril protein collagen VII reaches down into the dermal matrix. Anchoring fibres form solid structures whose functional role is to tie the lamina densa to the papillary dermis, where they attach to dermal collagen fibres made of types I, III and V collagen. At its N-terminal extremity, each triple helix of collagen VII is flanked by a globular NC1 domain. Two of these chains link at their C-terminal ends to form a dimer. These dimers are short striated fibrils that combine laterally to form anchoring fibrils. The collagen VII interacts with the other components of the extracellular matrix through its NC1 domain, attaching to the laminin-5 and anchoring the basal membrane to the dermis where it connects to the other types of collagen (I and III). It would appear that some genetic and orphan diseases may be due to an absence of collagen VII. Any molecule found in either one of the basal lamina and/or the reticular lamina such as collagen, proteoglycans and glycoproteins including laminins is called herein a DEJ molecule.
Aging of the skin results from two processes: (1) an intrinsic process, corresponding to chronological aging, and (2) an extrinsic process resulting mainly from the deleterious effect of exposure to the sun and environmental pollution.
Upon aging, major changes within connective components of the dermis can be seen: collagen looses its regular and fascicular appearance, while ground substance increases, elastic material decreases and the fibroblast cell population becomes “at rest”. Also, during the skin aging process, the DEJ progressively loses its ability to fulfill its mechanical function, resulting in a weakening of the epidermis-dermis interface. The resulting dermal aging is different according to individuals and is related to genetic background and exposition to multiple aggressions.
One of the objectives in cosmetological research is to control or prevent skin aging. Traditional approaches based on the supply of keratinocytes and the metabolism of fibroblasts are now known to be inadequate, particularly in light of recent data on the DEJ.
Therefore, this is a need to develop new approaches for the prevention and/or treatment of skin condition such as the aging of the skin.